An international expert panel has consolidated the phase 3 data, the FDA labels and early clinical experience for resmetirom and semaglutide into one practice update for metabolic dysfunction-associated steatohepatitis with significant fibrosis (F2-F3) and no cirrhosis - the first time this disease has had pharmacological treatment at all. The two agents work differently: resmetirom is a liver-directed thyroid hormone receptor-beta agonist, semaglutide a GLP-1 receptor agonist with broad metabolic effects.
The review covers the whole pathway rather than only drug choice: non-invasive test-based diagnosis of MASH with significant fibrosis, selecting and starting treatment, monitoring on treatment, and assessing response. It addresses the questions that actually arise in clinic - how to individualise by phenotype, what to do with a patient already on a GLP-1 receptor agonist for diabetes or obesity, and how to define response, non-response, and the criteria for switching or combining. The panel says explicitly that the framework will change as long-term outcome data arrive.
Two things to hold alongside it. Both approvals are conditional and rest on histological surrogate endpoints, not on cirrhosis, decompensation or death. And neither drug is straightforwardly available in India, where the practical pathway remains weight management, metabolic risk control and fibrosis staging - which is what the non-invasive diagnostic half of this document is genuinely useful for.
- Stage fibrosis non-invasively before considering either drug - F2-F3 without cirrhosis is the licensed population
- Check whether a patient is already on a GLP-1 receptor agonist before adding anything; the panel addresses this case directly
- Define response and non-response before starting, so the decision to switch is not made ad hoc
- Keep weight management and metabolic risk control as the base of the pathway, not as what you do if drugs are unavailable
- Tell patients the approvals are conditional and based on histology, not on survival
Why it matters
MASH has gone from having no drug treatment to having two with different mechanisms, and nobody had set out how to choose, monitor or switch between them.
Don't overread it
This is an expert panel synthesis, not new trial data - and both approvals rest on histological surrogates rather than clinical outcomes.
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